外泌体在治疗中枢神经系统疾病中的应用方向
Application of Exosomes in the Treatment of Central Nervous System Disorders: Current Perspectives
DOI: 10.12677/hjbm.2025.154092, PDF,   
作者: 陈骏发：中山大学附属第七医院手术麻醉中心，广东 深圳
关键词: 外泌体；中枢神经系统疾病；miRNA；生物标志物；工程化外泌体；Exosomes； Central Nervous System Diseases； miRNA； Biomarkers； Engineered Exosomes
摘要: 外泌体作为内体来源的细胞外囊泡(40~160 nm)，携载核酸、蛋白质及脂质等生物活性分子，具有穿越血脑屏障、靶向递送物质的独特优势，在中枢神经系统(CNS)疾病治疗中展现出巨大潜力。本综述系统总结其应用进展：在创伤性脑损伤(TBI)中，间充质干细胞源外泌体(如BMSCs-Exos、ADSCs-Exo)通过递送miR-124-3p、circ-Scmh1等分子，抑制NLRP3炎症小体活化及谷氨酸兴奋毒性，促进神经再生；在缺血性卒中领域，外泌体调控miR-145、miR-760-3p等减轻脑缺血再灌注损伤，增强血管新生与运动功能恢复；针对神经退行性疾病，外泌体不仅参与阿尔茨海默病(AD)的β-淀粉样蛋白清除调控(如工程化Fe65-exos)，还可通过富含miR-23b-3p的囊泡促进帕金森病(PD)神经元自噬与线粒体功能修复；在自身免疫性疾病中，嵌合CNS靶向肽外泌体(TAxI-exos)可调节Th/Treg免疫平衡，缓解实验性脑脊髓炎；此外，外泌体作为天然纳米载体可突破血脑屏障递送抗肿瘤药物(如miR-124-3p)，抑制胶质瘤生长并预警脑转移。尽管临床前研究证实其神经保护与再生效能显著，但标准化分离、载药优化及临床转化仍需突破。工程化外泌体与无细胞治疗策略有望成为CNS疾病治疗的新范式。
Abstract: Exosomes, endosome-derived extracellular vesicles (40~160 nm), carry bioactive molecules including nucleic acids, proteins, and lipids. Their unique capacity to cross the blood-brain barrier (BBB) and achieve targeted substance delivery positions them as promising therapeutic agents for central nervous system (CNS) disorders. This review systematically summarizes recent advances: In traumatic brain injury (TBI), mesenchymal stem cell-derived exosomes (BMSCs-Exos, ADSCs-Exo) deliver molecules such as miR-124-3p and circ-Scmh1 to suppress NLRP3 inflammasome activation and glutamate excitotoxicity while promoting neural regeneration. For ischemic stroke, exosomes mitigate cerebral ischemia-reperfusion injury by regulating miR-145 and miR-760-3p, enhancing angiogenesis and motor function recovery. In neurodegenerative diseases, engineered Fe65-exosomes facilitate β-amyloid clearance in Alzheimer’s disease (AD), while vesicles enriched with miR-23b-3p promote neuronal autophagy and mitochondrial function restoration in Parkinson’s disease (PD). For autoimmune disorders, chimeric CNS-targeting peptide exosomes (TAxI-exos) modulate Th/Treg immune balance, alleviating experimental autoimmune encephalomyelitis. As natural nanocarriers, exosomes overcome the BBB to deliver antitumor agents (miR-124-3p), inhibiting glioma progression and detecting brain metastases. Despite significant neuroprotective and regenerative efficacy in preclinical studies, challenges remain in standardized isolation, drug-loading optimization, and clinical translation. Engineered exosomes and cell-free therapeutic strategies represent emerging paradigms for CNS disease treatment.
文章引用：陈骏发. 外泌体在治疗中枢神经系统疾病中的应用方向[J]. 生物医学, 2025, 15(4): 867-878. https://doi.org/10.12677/hjbm.2025.154092

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